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Relationship Between Stress-Induced Myocardial Ischemia and Atherosclerosis Measured by Coronary Calcium Tomography Daniel S

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Relationship Between Stress-Induced Myocardial Ischemia and Atherosclerosis Measured by Coronary Calcium Tomography Daniel S Journal of the American College of Cardiology Vol. 44, No. 4, 2004 © 2004 by the American College of Cardiology Foundation ISSN 0735-1097/04/$30.00 Published by Elsevier Inc. doi:10.1016/j.jacc.2004.06.042 EXPEDITED REVIEW Relationship Between Stress-Induced Myocardial Ischemia and Atherosclerosis Measured by Coronary Calcium Tomography Daniel S. Berman, MD, FACC,*† Nathan D. Wong, PHD, FACC,‡ Heidi Gransar, MS,*† Romalisa Miranda-Peats, MPH,*† John Dahlbeck, BS,*† Sean W. Hayes, MD,*† John D. Friedman, MD, FACC,*† Xingping Kang, MD,*† Donna Polk, MD, MPH,*† Rory Hachamovitch, MD, FACC,§ Leslee Shaw, PHD,*† Alan Rozanski, MD, FACC*† Los Angeles and Irvine, California OBJECTIVES We assessed the relationship between stress-induced myocardial ischemia on myocardial perfusion single-photon emission computed tomography (MPS) and magnitude of coronary artery calcification (CAC) by X-ray tomography in patients undergoing both tests. BACKGROUND There has been little evaluation regarding the relationship between CAC and inducible ischemia or parameters that might modify this relationship. METHODS A total of 1,195 patients without known coronary disease, 51% asymptomatic, underwent stress MPS and CAC tomography within 7.2 Ϯ 44.8 days. The frequency of ischemia by MPS was compared to the magnitude of CAC abnormality. RESULTS Among 76 patients with ischemic MPS, the CAC scores were Ͼ0 in 95%, Ն100 in 88%, and Ն400 in 68%. Of 1,119 normal MPS patients, CAC scores were Ͼ0, Ն100, and Ն400 in 78%, 56%, and 31%, respectively. The frequency of ischemic MPS was Ͻ2% with CAC scores Ͻ100 and increased progressively with CAC Ն100 (p for trend Ͻ0.0001). Patients with symptoms with CAC scores Ն400 had increased likelihood of MPS ischemia versus those without symptoms (p ϭ 0.025). Absolute rather than percentile CAC score was the most potent predictor of MPS ischemia by multivariable analysis. Importantly, 56% of patients with normal MPS had CAC scores Ն100. CONCLUSIONS Ischemic MPS is associated with a high likelihood of subclinical atherosclerosis by CAC, but is rarely seen for CAC scores Ͻ100. In most patients, low CAC scores appear to obviate the need for subsequent noninvasive testing. Normal MPS patients, however, frequently have extensive atherosclerosis by CAC criteria. These findings imply a potential role for applying CAC screening after MPS among patients manifesting normal MPS. (J Am Coll Cardiol 2004;44:923–30) © 2004 by the American College of Cardiology Foundation An increasing body of literature demonstrates that measure- detecting CAD in patients with an intermediate likelihood ment of coronary artery calcification (CAC) by X-ray of this condition, and for nearly as long it has been established computed tomography (CT), using either electron beam as highly effective for risk stratification of patients with an computed tomography (EBCT) or multislice spiral com- intermediate or high likelihood of CAD (11–19). Thus, stress puted tomograpy (MSCT), represents a potent means for MPS is now commonly used for shaping key clinical manage- improving the diagnostic assessment and risk stratification ment decisions among patients with suspected or known of patients with suspected coronary artery disease (CAD) CAD, such as distinguishing which CAD patients are likely to (1–10). Hence, the applications of this newer technology benefit from coronary revascularization versus medical man- may overlap some of the clinical applications associated with agement (20). The wide use and ubiquitous presence of noninvasive stress tests. For instance, for nearly three noninvasive stress tests, such as MPS, coupled with the decades, stress myocardial perfusion single-photon emission increasingly recognized utility and growing availability of CAC computed tomography (MPS) has been widely utilized for scanning, raises a new clinical problem for clinicians: how should CAC scanning be integrated with conventional stress imaging tests into the clinical assessment of patients with From the *Departments of Imaging and Medicine and the Burns and Allen Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, †Depart- suspected and known CAD? Understanding the potential ment of Medicine, David Geffen School of Medicine, University of California, Los predictive relationship between CAC levels and the likelihood Angeles, California; ‡Heart Disease Prevention Program, University of California, of stress-induced myocardial ischemia would be central to Irvine, California; and the §Division of Cardiology, Keck School of Medicine, University of Southern California, Los Angeles, California. This study was supported addressing this question. Thus, we undertook the present study by a grant from the Eisner Foundation, Los Angeles, California. Dr. John J. to examine the potential inter-relationship between the pres- Mahamarian acted as Guest Editor for this paper. Manuscript received January 15, 2004; revised manuscript received June 14, 2004, ence and magnitude of CAC and the presence and magnitude accepted June 15, 2004. of inducible myocardial ischemia during stress MPS. 924 Berman et al. JACC Vol. 44, No. 4, 2004 MPS and EBCT August 18, 2004:923–30 reduced workload. Tc-99m sestamibi MPS imaging was Abbreviations and Acronyms begun 15 to 30 min after radioisotope injection (21). CAC ϭ coronary artery calcium Adenosine MPS protocol. In 146 (12%) of the study CAD ϭ coronary artery disease subjects, adenosine stress was performed (22). Patients were ϭ CT computed tomography instructed not to consume caffeine products for 24 h before EBCT ϭ electron beam computed tomography ϭ MPS. Following rest MPS, adenosine was infused (140 HU Hounsfield units ␮ MPS ϭ myocardial perfusion single-photon emission g/kg/min for 5 to 6 min), and Tc-99m sestamibi was computed tomography injected at the end of the 2nd or 3rd min of infusion for the MSCT ϭ multislice spiral computed tomography 5- and 6-min infusions, respectively. In patients who could ϭ SDS summed difference score tolerate it, low-level treadmill exercise, as an adjunct to SPECT ϭ single-photon emission computed tomography SRS ϭ summed rest score adenosine infusion, was performed at 0% to 10% grade, at 1 SSS ϭ summed stress score to 1.7 miles/h. The Tc-99m sestamibi MPS was initiated Tc ϭ technetium approximately 60 min after the end of adenosine infusion in Tl ϭ thallium patients who did not exercise and 15 to 60 min after injection in those with adjunctive exercise. METHODS During both types of stress, blood pressure was recorded at rest, at the end of each stress stage, and at peak stress. We evaluated 1,195 patients who underwent rest/stress dual Maximal ST-segment change was assessed as horizontal, isotope MPS and CAC scanning by EBCT (Imatron upsloping, or downsloping, and electrocardiographic ischemia C-150 or GE e-Speed, GE-Imatron Inc., South San was defined as ST-segments Ն1 mm horizontal or downslop- Francisco, California) or MSCT (Siemens Volume Zoom, ing or Ն1.5 mm upsloping at 80 ms after the J point. Siemens Medical Systems, Forchheim, Germany) at SPECT acquisition protocol. The MPS studies were Cedars-Sinai Medical Center within six months of each performed on multidetector scintillation cameras using an other (7.2 Ϯ 44.8 days). The mean age of the study elliptical 180° acquisition for 60 to 64 projections at 20 s per population was 58.4 Ϯ 10.3 years, and 869 (72.7 %) of the projection (21). For Tl-201, two energy windows were used, patients were male. Patients underwent MPS on a clinical including a 30% window centered on the 68- to 80-keV basis, and CAC imaging was performed either on a basis of peak and a 10% window centered on the 167 keV peak. For self-referral (n ϭ 94 patients), physician-referral (n ϭ 777 Tc-99m sestamibi, a 15% window centered on the 140-keV patients), or ongoing research (n ϭ 324 patients) in the peak was used, and images were obtained in both supine and Early Identification of Subclinical Atherosclerosis by Non- prone positions. For supine rest and stress MPS studies, gated invasive Imaging Research (EISNER) study. Exclusion SPECT was performed, obtaining 8 to 16 frames/cycle. criteria included prior coronary bypass surgery or percuta- Images were acquired using a 64 ϫ 64 image matrix and were neous coronary intervention, history of myocardial infarc- subject to quality control measures as previously described (21). tion, known valvular heart disease, or primary cardiomyop- No attenuation or scatter correction was employed. athy. This research was approved by the Cedars-Sinai Interpretation of SPECT. Semiquantitative visual interpre- Medical Center Institutional Review Board. tation was performed using 20 segments for each image set. Imaging and stress protocol. Patients were injected intra- Segments were scored by consensus of two experienced ob- venously at rest with thallium-201 (Tl-201) (3.0 to 4.5 servers using a 5-point score (0 ϭ normal, 1 ϭ equivocal, 2 ϭ mCi) with dose variation based on patient weight. Rest moderate, 3 ϭ severe reduction of radioisotope uptake, and 4 Tl-201 SPECT was initiated 10 min after injection of the ϭ absence of detectable tracer uptake in a segment) (21). radionuclide (21). Scintigraphic indices. The summed stress score (SSS) and Exercise MPS protocol. Following rest MPS, symptom- summed rest score (SRS) were obtained by adding the limited Bruce protocol treadmill exercise testing was per- scores of the 20 segments of the respective images (19). An formed in 1,049 (88%) of the 1,195 study subjects. Exercise SSS Ն4 was considered abnormal (21). The sum of the end-points included physical exhaustion, severe angina, differences between each of the 20 segments from these sustained ventricular tachycardia, hemodynamically signifi- images was defined as the summed difference score (SDS), cant supraventricular dysrhythmias, or exertional hypoten- incorporating assessment of both the extent and severity of sion. In accordance with our policy to discontinue anti- stress-induced myocardial ischemia, each of which indepen- ischemic medications before exercise testing, only 36 dently adds prognostic information (11).
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